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Abstract:

The initial chapters of this thesis describe the clinical and physiological aspects of hypoglycaemia, followed by a review of the literature on the effects of acute hypoglycaemia on cognitive function. The subsequent chapters describe original research studies in subjects with and without diabetes, which examine the effects of acute hypoglycaemia on aspects of cognitive function and the prevention of hypoglycaemia. In Studies 1 to 3, a hyperinsulinemic glucose clamp was used to either maintain euglycemia (blood glucose 4,5 mmol/l) or induce hypoglycaemia (2.6 mmol/l) in both healthy adults (n=20), and subjects with type 1 diabetes (n=16). A cognitive test battery was administered to examine aspects of attention, intelligence, motivation, affect and subjective cognition. Hypoglycaemia induced a significant deterioration in tests sensitive to both visual and auditory selective attention, and attentional flexibility deteriorated (Studies 1 and 2). Intelligence scores did not deteriorate during hypoglycaemia (Studies 1 and 2). In Study 3, hypoglycaemia increased task-irrelevant interference and self-focus of attention, but motivation declined to a similar extent during both study conditions. Hypoglycaemia produced a negative mood state with a significant fall in energy levels and a concomitant rise in anxiety (Study 3). Study 4 was an open-label, comparative study of the post-prandial glucodynamics of insulin lispro, when administered either 5 minutes before or 20 minutes after a high fat/high solid phase meal, in twelve subjects with type 1 diabetes. Administration of insulin lispro after the meal reduced the risk of early postprandial hypoglycaemia, without compromising postprandial glycaemic control. Therefore, the work in this thesis has demonstrated a different deterioration of attentional function in humans during hypoglycaemia with no effect on non-verbal reasoning skills. Furthermore, it would appear that the brain is not only less cognitively competent and more dysphoric during hypoglycaemia, it is also more self-aware and distracted when required to perform effortful processing.